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Moreover, the development of structural derivatives using natural products as lead compounds constitutes a crucial strategy for discovering new fungicides, which has garnered significant interest from researchers worldwide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In this study, we designed a series of novel isocryptolepine derivatives via structural simplification of the parent isocryptolepine. These compounds were synthesized and evaluated for antimicrobial efficacy against plant pathogens. Several derivatives showed higher activity than positive control drug. Notably, compound\n                      <jats:bold>Y\u2010D\u201029<\/jats:bold>\n                      exhibited outstanding potency with minimum concentration inhibiting 90% bacterial growth values of 3.12\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      against\n                      <jats:italic>Xoo<\/jats:italic>\n                      and\n                      <jats:italic>Xac<\/jats:italic>\n                      , surpassing the benchmark agricultural bactericide thiodiazole copper. Mechanistic studies indicated that\n                      <jats:bold>Y\u2010D\u201029<\/jats:bold>\n                      inhibited bacterial biofilm formation and significantly reduced exopolysaccharide production in\n                      <jats:italic>Xoo<\/jats:italic>\n                      . Furthermore, propidium iodide and reactive oxygen species (ROS) staining revealed that\n                      <jats:bold>Y\u2010D\u201029<\/jats:bold>\n                      disrupted cell membrane integrity and induced lipid peroxidation along with intracellular ROS accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      Our study indicated that the simplified isocryptolepine analogues, especially\n                      <jats:bold>Y\u2010D\u201029<\/jats:bold>\n                      , are promising broad\u2010spectrum antibacterial agents for plant disease management. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  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